A 3D numerical approach using the Finite Element Method (FEM) is applied to model the thermal behavior of multilayer 20Ah LiFePO4/Graphite cell and to design a cooling system. A three-dimensional multilayer cell model with heterogeneous thermal properties for the various cell layers is developed to study the effects of design parameters on cooling performance of mini-channel aluminum plates. As design parameters, effects of channel width, a number of channel passes, inlet mass flow rate, and heat transfer medium were considered. Using the optimized parameters, the cooling performance of water-cooling and air-cooling systems were compared. The results showed that the designed cooling system provided good cooling performance in controlling the temperature rise and uniformity. Inlet mass flow rate was the main influential parameter in controlling the cooling performance. The optimum number of channel passes was found to be seven passes. Channel width mainly controlled the pressure drop and had minor effects on temperature. At higher discharge current rates, the water-cooling system showed better cooling performance in dropping the maximum temperature and making uniform surface and inner temperature profile. Moreover, pressure drop, and power consumption rates become significantly lower for water cooling system.